Silymarin/Silybin and Chronic Liver Disease: A Marriage of Many Years

Federico, Alessandro; Dallio, Marcello; Loguercio, Carmelina

doi:10.3390/molecules22020191

Cited by 348 publications

(253 citation statements)

References 140 publications

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“…Positive roles of silymarin were showed on nonalcoholic steatohepatitis, nonalcoholic fatty liver disease, and fibrosis in experimental human hepatocytes. Silybin interferes in oxidative stress, accumulation of fat in liver, and insulin resistance (Federico, Dallio, & Loguercio, ; Marin et al, ). It improves functional liver tests (Aller et al, ) and leads to a reduction in hepatotoxicity induced by high doses of acetaminophen and can diminish oxidative stress in mice (Brandon‐Warner et al, ; Papackova et al, ).…”

Section: Introductionmentioning

confidence: 99%

Safety and toxicity of silymarin, the major constituent of milk thistle extract: An updated review

Soleimani

Delghandi

Moallem

et al. 2019

Phytotherapy Research

155

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Milk thistle (Silybum marianum) is a medicinal plant from the Asteraceae family. Silymarin is the major constituent of milk thistle extract and is a mixture of some flavonolignans such as silybin, which is the most active component of silymarin. It is most commonly known for its hepatoprotective effect. Also, studies have shown other therapeutic effects such as anticancer, anti‐Alzheimer, anti‐Parkinson, and anti‐diabetic, so its safety is very important. It has no major toxicity in animals. Silymarin was mutagen in Salmonella typhimurium strains in the presence of metabolic enzymes. Silybin, silydianin, and silychristin were not cytotoxic and genotoxic at concentration of 100 μM. Silymarin is safe in humans at therapeutic doses and is well tolerated even at a high dose of 700 mg three times a day for 24 weeks. Some gastrointestinal discomforts occurred like nausea and diarrhea. One clinical trial showed silymarin is safe in pregnancy, and there were no anomalies. Consequently, caution should be exercised during pregnancy, and more studies are needed especially in humans. Silymarin has low‐drug interactions, and it does not have major effects on cytochromes P‐450. Some studies demonstrated that the use of silymarin must be with caution when co‐administered with narrow therapeutic window drugs.

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Section: Introductionmentioning

confidence: 99%

Safety and toxicity of silymarin, the major constituent of milk thistle extract: An updated review

Soleimani

Delghandi

Moallem

et al. 2019

Phytotherapy Research

155

View full text Add to dashboard Cite

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“…In addition, anticancer, cardioprotective, neuroprotective, UV-protective, hypocholesterolemic and some other effects have been reported for silymarin in animal models [4], [5], [6], [7]. Although a wide range of molecular targets have been identified in vitro for individual flavonolignans, the protective potential of silymarin is primarily attributed to its antioxidant action [4], [7], [8].…”

Section: Introductionmentioning

confidence: 99%

Flavonolignan 2,3-dehydrosilydianin activates Nrf2 and upregulates NAD(P)H:quinone oxidoreductase 1 in Hepa1c1c7 cells

et al. 2017

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Silybum marianum (milk thistle) is a medicinal plant used for the treatment of various liver disorders. This study examined whether the main flavonolignans from S. marianum (i.e. silybin, silychristin, silydianin) and their 2,3-dehydro derivatives (i.e. 2,3-dehydrosilybin, 2,3-dehydrosilychristin, 2,3-dehydrosilydianin) activate the Nrf2 pathway, which regulates the expression of genes encoding many cytoprotective enzymes, including NAD(P)H:quinone oxidoreductase 1 (NQO1). After 48 h of exposure, 2,3-dehydrosilydianin at concentrations of 25 μM and higher significantly elevated the activity of NQO1 in murine hepatoma Hepa1c1c7 cells. In contrast, other tested compounds at non-cytotoxic concentrations had a mild or negligible effect on the NQO1 activity. Using a luciferase reporter assay, 2,3-dehydrosilydianin was found to significantly activate transcription via the antioxidant response element in stably transfected human AREc32 reporter cells. Moreover, 2,3-dehydrosilydianin caused the accumulation of Nrf2 and significantly induced the expression of the Nqo1 gene at both the mRNA and protein levels in Hepa1c1c7 cells. We found that 2,3-dehydrosilydianin also increased to some extent the expression of other Nrf2 target genes, namely of the heme oxygenase-1 gene (Hmox1) and the glutamate-cysteine ligase modifier subunit gene (Gclm). We conclude that 2,3-dehydrosilydianin activates Nrf2 and induces Nrf2-mediated gene expression in Hepa1c1c7 cells.

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“…Silymarin, extract of milk thistle seeds, has been widely used in various liver disorders mainly because of its antioxidant and anti-inflammatory activity [112,113]. Silymarin is classified as BCS class II or IV agent with poor water-solublility and low intestinal permeability [114].…”

Section: Silymarin and Dehydrosilymarinmentioning

confidence: 99%

Liposomes for Enhanced Bioavailability of Water-Insoluble Drugs: In Vivo Evidence and Recent Approaches

Lee

2020

Pharmaceutics

177

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It has been known that a considerable number of drugs in clinical use or under development are water-insoluble drugs with poor bioavailability (BA). The liposomal delivery system has drawn attention as one of the noteworthy approaches to increase dissolution and subsequently absorption in the gastrointestinal (GI) tract because of its biocompatibility and ability to encapsulate hydrophobic molecules in the lipid domain. However, there have been several drawbacks, such as structural instability in the GI tract and poor permeability across intestinal epithelia because of its relatively large size. In addition, there have been no liposomal formulations approved for oral use to date, despite the success of parenteral liposomes. Nevertheless, liposomal oral delivery has resurged with the rapid increase of published studies in the last decade. However, it is discouraging that most of this research has been in vitro studies only and there have not been many water-insoluble drugs with in vivo data. The present review focused on the in vivo evidence for the improved BA of water-insoluble drugs using liposomes to resolve doubts raised concerning liposomal oral delivery and attempted to provide insight by highlighting the approaches used for in vivo achievements.Pharmaceutics 2020, 12, 264 2 of 30 However, there have been several drawbacks to be overcome, such as instability in the GI tract and poor permeability across the intestinal epithelia because of liposomes' relatively large size [8]. Moreover, it seemed that liposomal oral delivery was faltering during 1980s due to some disappointing results for insulin [9]. However, liposomal oral delivery resurged with a rapid increase in the number of papers published, as shown in Pubmed search results, mainly due to various advanced modification technologies, even though liposomal oral delivery-related papers account for only 5-6% of the total number of liposomes-related studies (Figure 1). In addition, there was an encouraging meta-analysis report in which phospholipid-based solid formulations were analyzed as being effective for BA enhancement [10]. Although liposomal delivery does not seem to achieve satisfactory improvement of oral BA for peptides and protein drugs yet, it looks more promising for oral delivery of hydrophobic drugs because liposomes can solubilize poorly water-soluble drugs, protect the drug from degradation in the GI tract and enhance permeability through the epithelial cell membrane, consequently increasing oral BA. However, most published papers performed in vitro studies only, thus lacking in vivo pharmacokinetic results. The present review focuses on the in vivo evidence for the improved BA of water-insoluble drugs and highlights the approaches used for in vivo achievements.

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Silymarin/Silybin and Chronic Liver Disease: A Marriage of Many Years

Cited by 348 publications

References 140 publications

Safety and toxicity of silymarin, the major constituent of milk thistle extract: An updated review

Safety and toxicity of silymarin, the major constituent of milk thistle extract: An updated review

Flavonolignan 2,3-dehydrosilydianin activates Nrf2 and upregulates NAD(P)H:quinone oxidoreductase 1 in Hepa1c1c7 cells

Liposomes for Enhanced Bioavailability of Water-Insoluble Drugs: In Vivo Evidence and Recent Approaches

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